Is Too Much Safety Information A Bad Thing?
68 CommentsBy Ed Silverman // December 9th, 2008 // 8:51 am
You could get that impression from reading a piece this morning in The Wall Street Journal, which notes the FDA recently launched a new effort to alert consumers to safety issues, and a few drugmakers are now running web sites that attempt to communicate risks more openly. The paper, however, writes that consumers are receiving a “flood” of info that “risks scaring some people.”
“Too much information about drug safety - disseminated through media, online alerts from consumer watchdog groups and even by the Food and Drug Administration itself - might overwhelm patients and raise undue alarm,” according to some medical professionals who spoke with the paper. The problem - consumers may forget about benefits if they focus only on risk. And the consequences of stopping a med, particularly for a chronic condition, may be worse than the chance of a side effect.
A Pfizer survey of 300 medical professionals in March found that 89 percent of respondents were at least somewhat concerned that patients might stop their meds if potentially negative safety info was released to the public too early. The Journal cites one woman who says the Chantix smoking-cessation pill made her depressed and dropped it after reading an FDA advisory about suicidal thoughts.
And so the FDA plans to study how consumers react to and use safety info. Paul Seligman, an agency safety official, cites the debate over warnings about antidepressants, and whether these inadvertently contributed to a subsequent rise in suicide rates. The FDA also plans to revamp its early-communication letters to include more info, such as the number of adverse events compared to the number of people taking a drug. Alerts will be posted on the FDA and WebMD sites.
Meanwhile, Johnson & Johnson has a new site called Medversation for its Remicade arthritis drug that contains clinical data written in plain English about efficacy and detailed explanations of side effects. Pfizer recently launched a site and Wyeth is upgrading some. “It’s a higher priority to take even small (safety) signals even more seriously than we did before,” Geno Germano, head of Wyeth’s pharma unit, tells the Journal.
Such efforts may not be enough, at least for now. Many consumers have doubts about the safety of their meds - only 27 percent of the public feels “very confident” that prescription drugs sold in the US are safe; just over half feel that drugmakers do enough to test and monitor for safety, according to a study this year conducted by the Kaiser Family Foundation and Harvard School of Public Health, the paper writes.
Anne
Nope, too much info is not a bad thing. It’s called informed consent.
Salmon
There are of course benefits to the drug companies to this.
1. People become immune to the same warnings for everything no matter the frequency. As Syndrome says in The Incredibles, when everyone is super then no one is super.
2. Reporting of rare events will allow followup in that and similar individuals and if blood or tissue or other info can be obtained datamining for genetic differences to develop new drugs for illnesses that genetic defect either produces or protects against or tests to comarket for the toxicity.
3. Ammunition inthe over the hopefully coming battle over increased Congressional oversight and regulation.
4. Preemption, ’nuff said.
Salmon
Chris
Part of the problem with these discussions is the definition of the term ’safe’. Drugs makers use the term ’safe’ for most any drug approved by the FDA (ie in a large group of people, benefits exceed known risks); however, in other contexts such as promotion, safe is implied or perceived to be ‘without risks’ or ‘with negligible risks’.
pharma professioal
I am a big proponent of informed consent. but a WSJ column from a few weeks ago made me rethink that somewhat. (Power of Suggestion: When Drug Labels Make You Sick
Melinda Beck. Wall Street Journal. (Eastern edition). New York, N.Y.: Nov 18, 2008. pg. D.1 ) The point of the column is that learning about side effects can make them happen in some cases.
Justice in Michigan
Ed - Do you have a reference for the Kaiser study cited at the end? Much appreciated!
In general, the danger of “overwarning” has been stock rhetoric of the anti-liability, anti-consumers rights forces. Good studies are certainly welcome. So far, witness the use of SSRI numbers, it’s been almost all self-ideology and mythology.
Re: pharma prof’s point, the ‘nocebo’ effect is certainly real, just like the placebo effect. Since the majority of people (including physicians) ignore or dismiss what is on the label, it appears to be a weak force in the scheme of things.
Ed Silverman
Hi Justice,
Yes, I’ve just done so. Sorry about that. I overlooked the link before posting.
Cheers
ed
John Mack
It’s important to consider the other side of the “Fair Balance” sheet: benefit statements made in DTC ads.
DTC ads include a lot of benefit statements that may impress consumers just as effectively as risk statements scare them. In fact, I would contend that the benefit statements — especially when made by trusted celebrities like Sally Field — more than compensate for the side effect statements.
See my blog post “Scare Balance or Scare Tactics? A Weak Case Against More DTC Risk Information”: http://tinyurl.com/6678kc
Another point: pharma marketers may be getting around fair balance in Internet ads. See Death of the One-Click “Rule” or “Received Precedent” or Whatever!: http://tinyurl.com/6j8s3n
Nathan
Salmon,
You #1 point above is exactly why I am (marginally) in favor of preemption. I think that a financially independent review board is the only “fair” body to make decisions on the appropriate balance of risk and benifit presented in advertising and packaging. If you’ve taken the time to read any prescription inserts lately, you’ll realize that there seems to be a “cover-my-butt” mentality with side effects.
In other words, if we (pharma) can warn against virtually every plausible side effect, then consumers will learn to disreguard the safety information and (importantly) our “butts will be covered” when they choose to file a liability lawsuit. They were warned! They just chose to disreguard the warning….
*THAT* is why I believe that the ultimate arbirator for these decisions should be the FDA. If the FDA is the final authority for these decisions, then pharma can’t (and shouldn’t) be held liable when and if they screw up by over or under warning.
Justice in MI
Nathan - Your point makes sense if it were demonstrable. But when the FDA managers’ statements were recently uncovered in Waxman’s report - cited here - what we read Jenkins and others say is that companies fight _against_ additional warnings, even for the sake of CYA.
In my own reviews of negotiations between companies and FDA over labels - admittedly not a scientific sample - that is also what I found without exception
So this, too, appears to be mythological. Can anyone document a CYA-added warning?
harpy
“Too much information about drug safety - disseminated through media, online alerts from consumer watchdog groups and even by the Food and Drug Administration itself - might overwhelm patients and raise undue alarm,” according to some medical professionals who spoke with the paper.
I got five dollah says one of the medical professionals is Peter J. Pitts - any takers?
Salmon
Nathan, We’ll have to disagree. Your argument comes down to you trust the FDA. I don’t.
Salmon
Opinions are my own and do not represent the opinions of the FDA.
LILLI
Safety alerts only work if Congress madates that primary care doctors must monitor and report adverse side effects with medications. Most doctors do not tell you that your ankles are swolleb from high blood pressure medications–or stain medications are the cause of neuropathy—the emergency room doctor will not tell that the cause of renal failure is from the statins you have been taking for many years. And what about the the years you have been taking aspirins? Sometimes we do need medications but doctors must supervise them carefully—-all medications have lots of toxins that are causing serious side effects that lead to unexpected death beacuse doctors are and telling the truth and percribe more medications that interact and cause more problems.
Justice in Michigan
I trust THIS from FDA, because it was an internal communication not intended to see the light of day. It was posted by Ed previously and speaks directly to the argument Nathan asserts:
“Here’s reaction from Jane Axelrad, associate director for policy in the FDA’s Center for Drug Evaluation and Research, who wrote to agency political appointees: “There are continued references to sponsors ‘disclosing too much’ risk information and its adverse impact…We rarely find ourselves in situations where sponsors want to disclose more risk information than we think is necessary. To the contrary, we usually find ourselves dealing with situations where sponsors want to minimize the risk information.”
Nathan - I think this directly negates your point. What do you think?
Salmon
Justice,
I have done enough labeling to not even trust labeling that I’ve written and/or reviewed. There has been more than one case where I’ve realized a year or two later that the company hid information from me and I didn’t pick up on it initially. Unfortunately we have neither the time nor the administrative authority to go back and update labeling on our own as reviewers or as divisions. You hope that the company comes back in sometime with a different labeling change (ideally a new indication so you have some leverage) and you can try to fix it. Unfortunately they will drag out labeling changes like this for years and years arguing with you. Each time you give them your position they simply take a year to respond and then they disagree and you go another round.
Salmon
Opinions are my own and do not represent the opinions of the FDA
Justice in Michigan
Your reflections are appreciated by many of us, Salmon. In the same report Ed reported on here, it is noted that the “overwarning” folks sometimes fought companies themselves, at least as suggested by this excerpt:
“In 2007, FDA received two requests from manufacturers seeking to immediately add safety information to their drug labels. Both requests concerned new risks that were so significant they needed to be included in the highlights section of the label. However, in both instances, the manufacturers were prohibited from promptly updating the drug label.”
All of this suggests that, superimposed on companies’ “usual” battles over label changes, the effort of recent years to minimize warnings sometimes ran counter to companies’ own inclinations. In that context, preemption as advocated by the Office of Chief Counsel becomes a way “solve the problem.”
JimK
On overwarning:
I think the fact that as soon a adverse information is released on a particular drug the pharmaceutical industry tolls out the PR machine and commissions their own studies to demonstrate how the adverse study was wrong is Prima Facie evidence that the Pharmaceutical industry is not looking to overwarn but is only attempting to build ammunition for their case as to why additional warnings are not necessary.
PS: I see there is another Jim posting at this site so I changed to JimK.
Salmon
This issue of FDA not allowing companies to put warning information in their labeling has more to it than people realize.
Companies may come in with labeling changes e.g. drug interactions or additional precautions etc. that primarily serve to protect them legally, or cover up a problem they know, but are really insufficient or even worse misleading and could imply not a problem or a lessor degree of a problem than is the reality. Sometimes we’re afraid that’s exactly what the company is trying to pull so we want to take a look first in case we actually need to make the warning stronger.
In the division I work(ed) in we handle approximately 25% of the NDAs at FDA. Yet there were only 3 of us handling the entire review workload for my scientific discipline. (60% of my office for my scientific discipline were managers or working on projects for the drug companies so it’s not the money at least for new drug reviews it’s the allocation of resources).
Sometimes these labeling changes are simply put on the shelf and you get to it when you get to it. Others have a 6 month clock and are put it in the queue with everything else. Others are so simple that you can knock it off in a few minutes or an hour but then management doesn’t like it because the company doesn’t like it or it may effect another company, or it may establish a precedent that may not be desirable either for the company, or another company, or for even for patients.
Consequently you can knock the review off and yet it won’t be signed off for years and the jackets (each the size of a telephone book) are simply taking up space in your office. The new computer system is even worse for this because you don’t have anything physical to remind you a couple times a year to check and see if you can’t get this thing moving along and done finally.
Salmon
Opinions are my own and do not reflect the opinions of the FDA.
George
Why would someone post this to this thread months later?
“I am afraid to take Byetta now that I heard about the 4 or 6 deaths…I must say Byetta worked for me.”
http://www.pharmalot.com/2008/08/four-more-deaths-associated-with-byett/#comment-384204
Especially right after this article ran.
Nathan
Salmon,
Your 4:35am post (wow!) is exactly what I suspected. If that’s the case, then doesn’t preemption make some sense? When a company wants additional safety info displayed, it’s unclear to the FDA (and to the public) whether thier motives is genuine protection or whether thier motive is to “dilute” another safety issue that may be perfectly real. Therefore an “impartial” body (the FDA) has to make the final judgement call on the label wording. So should the company be largely off-the-hook for liability as long as they were honest with the FDA and provided all the relevant information needed?
Salmon
PREEMPTION MAKES NO SENSE.
It’s the company who hides the info in the first place. There would be no hold ups as it is if the companies were following the law but they don’t.
The FDA is currently so corrupt that they are intentionally causing the killing and maiming of people. I know. I’ve seen the data as have certain members of Congress. Preemption will take away any incentive at all to be forthcoming. It they (the former “Ethical Pharmaceutical Industry”) were forthcoming in the first place they wouldn’t have trouble with lawsuits.
Salmon - A Former FDA Reviewer
Nathan
Salmon,
I understand your feelings — but you just wrote in your earlier post that companies come to the FDA with proposed additional warnings AND THE EXTRA WARNINGS GET REJECTED!
So if we fail to add warnings, we get slapped with lawsuits. When we WANT to add warnings, we sometimes get shot down. (you just told us so) Or we end up adding so many warnings that warnings have lost thier relevance. It seems that the FDA is the final arbitrator. Why shouldn’t THEY be liable when the warnings aren’t appropriate?
If there were no FDA, then I agree that companies should be completely liable for the products that they sell and the way that they present the safety data. But when the FDA is the final authority - often rejecting changes that we want to make — then it seems that they should also bare much of the liability when things go wrong.
Salmon
Nathan,
I DID NOT SAY WARNINGS get rejected.
They will come in saying that a pharmacokinetic drug interaction is minor and no need to worry when there is a major pharmacodynamic interaction.
For example Olanzapine (Zyprexa) and Fluoxetine (Prozac) is marketed as the combination Symbyax. Lilly got this by the reviewer but it’s clear that this will definitely cause a Phen-Fen type reaction. FDA upper management put out a minor press comment after the approval when someone on the outside observed something but didn’t tell the staff reviewers.
Other companies may come in with PK drug interacton studies for their SSRI’s and or Atypicals. From what I’ve seen I believe FDA management has been aware of this lethal interaction and is involved in hiding it not only from the public but from reviewers. You want a free pass on intentional maiming.
Here is a clear example that Preemption is simply nothing but fraud.
Jaynesday
George, ya gotta wonder don’t you. If it’s as both you and I suspect, it shows that the battle field of public opinion for pharma is right here and is not very ethical.
We see advances on a few fronts recently. One front is the overwarning issue. Another is the evil liability lawyer issue or that if Levine is lost by pharma, over night the industry will see an unbearable rash of lawsuits. Also some are making it appear that those against preemption are forcing the changes in drug safety while in fact preemption is the new kid on the block seeking to turn things upside down.
Nathan
Thanks Salmon. It seems that I’m the only one here who thinks that overwarning can be a problem…
It seems to me very logical that, in the current environment, a company would load up the safety precautions with all sorts of garbage just to hide the real dangers or just to overwhelm patients and make them think that the warnings are meaningless. I suppose no one else really agrees with that assertion.
(I’ll take this opportunity to, once again, point to my favorite example of this:
http://www.fda.gov/cder/foi/label/2004/17581s99,100,18164s50,51,18965s9,10,20067s4,6lbl.pdf
read pages 16-18 for a list of countless adverse reactions for this very dangerous over-the-counter drug…)
atlex
Nathan,
You are not alone. However, there are some battles that aren’t worth fighting on this site. There can be legitimate and thorough transparency without overstating safety information and, subsequently, compromising patient care. That’s what we should strive for as opposed to out-of-context listings of any and all possible side effects.
Atlex
Salmon
Nathan,
WARNINGS are a specific section of the labeling. You are lumping the entire labeling together under warnings. To some extent I agree that there’s a problem with information overload in labeling and the need to highlight the most important stuff. The new Physician Labeling Rule format makes an attempt at that although it has deficiencies. However the new labeling rules also in my opinion are clearly designed to eliminate critical infromation. There is no perfect answer.
Preemption however is simply a clear mechanism by which certain companies are attempting to prevent accounting for wrongs that those companies know that they did. Preemption is not about labeling or safety. Preemption is about money.Look at the statement from Lilly in Trends in Medicine from June 2004. However I’m certain there will be secondary consequences increasing unsafe drugs.
If companies want to have a defense against lawsuits then have them follow the law as it is now and actually give FDA the information they actually have and let us honestly decide what and how things go in the labeling. It simply doesn’t occur and until it does and it can be guarenteed that it will always occur honestly I will be against preemption.
Lawyers say if a law can be abused, it will be abused.
Justice in MI
Atlex - I think you are dismissing the possibility of learning on this site way too soon. Indeed, your own statement is an example - I am assuming you are saying it is not only an ideal, but is normative, yes?
The assumption that companies defensively overwarn (which you seem to disagree with, unless I misunderstood what you wrote) is a very common one. Indeed, I have heard it expressed by one of the best known anti-preemption lawyers.
That is why the views of someone like Jane Axelrad, not intended to be public, are so important. My lawyer friend, who is no naif, was himself surprised to hear it.
No doubt there are instances of everything, so we are really talking about overall trends. When an article of faith (on many sides) suddenly seems not so clear after all, it is always worth looking at.
Salmon
Nathan,
You also make my point for me. Please do take a look at the pages you mention. The symptoms with asterixes are those that can be associated with Pulmonary Arterial Hypertension the lethal Phen-Fen type toxicitie., Which should be mentioned as a concern, yet the labeling doesn’t. Why hasn’t the company mentioned this? This is clearly deficient labeling but it’s been reviewed and will allow for preemption. As for OTC. OTC approval is for lower doses and shorter durations and this is the labeling for the prescipition strength and duration usage for indications like rheumatoid arthritis, where those symptoms are most worrysome when they occur on prolonged usage or in a person with an underlying risk.
Nathan you claimed you’re in the industry and in development. Well it seems that all your examples etc. are just too convenient and leave out critical information. This is typically how corrupt drug companies work and why preemption should never be.
By the way if you work in the industry how can you spend all your day posting on this site? Are you being paid and if so what are you being paid to do?
You or Atlex tried to ask me that question before, well I was on indefinite suspension for talking to Congress. What about you?
Salmon - A soon to be former FDA whistleblower.
Opinions are my own and do not represent the FDA.
Nathan
Salmon writes:
“By the way if you work in the industry how can you spend all your day posting on this site?”
That’s one way to stop the conversation. If you don’t want to respond to me, then fine. But I’d rather you not judge how I spend my time. You obviously have plent of time to write things here as well.
By the way, I’m in research - not development. There’s a big difference. I do very early stage stuff and I learn most of what I know about late stage development from websites like this one.
atlex
Justice,
I’m not dismissing the concept of learning from postings on this site. What I suggested to Nathan was that he has more folks who agree with him than he may recognize. Many of us choose not to fight every fight for a variety of reasons (eg, we actually have jobs in corporations and have to take care in posting due to ridicule from the nutty fringe (not targeted at you), who have gone as far as trying to track us down and send personal emails.)
As for companies defensively overwarning…my intent is not to suggest that companies do or do not defensively overwarn. What I am suggesting is that most who write on this site and comment in public, including members of congress, have a simplistic view of what it means to provide safety information. They don’t understand how difficult it is to effectively provide information in a way that is transparent, but doesn’t lead to misperceptions and poor healthcare decisions.
Atlex
Salmon
Atlex,
Have you ever written labeling and if so what part did you play and what parts of the labeling did you write?
Justice in Michigan
Atlex, I appreciate your point. So here is a question, and the example is an arbitrary one (i.e., there are many from which one could choose).
As most of the media reported it, the Vioxx label change was mainly a story about Merck’s being able to stall for so many months, and then winning a relatively minor mention of VIGOR in “Precautions” rather than “Warnings,” etc. It was primarily the Wall Steet Journal (of all folks) who brought us the emails suggesting Ed Skolnick’s response to this result, the estimate of how much money it might save the company, some at FDA’s frustrations witht the company, and so on.
As Wyeth also did re: dodging a black box with fen-phen, Merck’s response was that it was only trying to do precisely what you describe:
“[E]ffectively provide information in a way that is transparent, but doesn’t lead to misperceptions and poor healthcare decisions.”
In _these_ situations, the average person following the stories comes away cynically, at best. I respectfully ask how you would respond. Do they not “get it”? Are they overgeneralizing from particular instances? Something else? Thanks.
atlex
Salmon,
I have never written and will never write labels. I have, at one point in my career developed content for adherence programs and struggled with how to accurately present risk and benefit information in a way that fully informs while not driving patients to noncompliance. As many social scientists recognize, the laypersons evaluation of risks is typically not particularly accurate. I don’t advocate anything but transparency, but I do advocate for development of better means of communicating risks to patients so they can truly make better healthcare decisions. Unfortunately, the system the way its currently built discourages this.
Atlex
atlex
JiM,
Unfortunately, while I don’t disagree with aspects of your point, you make an assumption in your posting that I fundamentally disagree with. You write about the average person coming away from the fen-phen and Vioxx situation cynical. This makes the assumption that the average person is paying attention. It also assumes that the media (and web) accurately portrays the situations. Frankly, I think if you conducted a poll, you’d find out that most Americans aren’t even that aware of these situations or, at best, vaguely aware, but don’t understand the situations.
In the end, though, I’m not sure how your question relates to my point which is that it is extremely difficult to communicate health information–benefits and risks. We need to find a better way to do it and just because we haven’t find the perfect way to communicate to all of the various stakeholders doesn’t mean that industry and others aren’t trying.
Atlex
Salmon
Atlex,
I understand the difficulty coming from what you describe you do. For others labeling includes any written or visual matter about the drug, including the container. When we are talking about preemption we are mainly interested in the implications on the professional labeling and any additional patient education labeling.
I have written or editted the latter types of labeling for many different classes of drugs both in industry and at FDA. In total actually dozens of new labels and hundreds of labeling updates. Due to my background and expertise I have worked on all aspects including chemisty, animal pharmalogy, clinical studies, safety (adverse events warning, precautions), special populations (pregancy elderly), clinical pharmacology, drug interactions, indications and usage, and the patient labeling.
In May 2007 I was told that an internal FDA committee reviewing all the pediatric labeling done to that point had unanimously agreed that pediatric labeling that I had written from scratch (because the company’s labeling was so bad) was the best example of pediatric labeling they had seen.
I raise this only to give you an indication that when I talk about labeling and whether FDA labeling should preempt lawsuits I speak from experience.
I am constantly fighting against being deceived by drug companies and I don’t always figure it out or when I do, in my view I get inappropriately overridden. In some cases this becomes apparent very shortly and FDA has to go through several iterations of updating safety language before it’s even close to what I originally recommended. To write the professional labeling is easier, but even here we can’t communicate the truly important information.
Patient directly labeling is much harder to write but it generally says talk to the prescriber or pharmacist (i.e. a learned intermediary) so as to avoid both overwarning and information overload. So my concern with preemption is really the prescriber information and that the prescriber will not have adequate information to make a decision or to talk to the patient intelligently.
There are many cases in even recent labeling where I know it is insufficient because the prescriber isn’t given critical information (such as the metabolite for this drug that effects a certain receoptor with known toxicities or even better explaining what those toxicities are so they can be monitored for. These things will not scare patients off. They probably won’t even know but the physician will know to monitor.
Preemption will take away companies being held accountable when they have intentionally withheld information from the FDA and/or the company and FDA has withheld information from the practicing physician. That should never be. As for preemption with a fraud provision. I don’t believe there is simply anyway for anyone to show fraud unless a reviewer releases information to the public on their own.
Salmon
Opinions are my own and do not represent the positions of the FDA.
Jaynesday
Alex, Salmon, JiM, Nathan et all
Could we not find a way to have a real time report on drug/device affects including trends of AE’s go out to doctors and patients for a better means to decide what to prescribe or not prescribe? A static label seems like a silly concept when it is based on limited trials that apparently sometimes don’t translate well in real life.
David
Industry is trying to find a way to communicate risks as long as that communication does not negatively impact sales.
Just A Thought
Drug companies want to market to consumers but they don’t trust them to be able to handle the information. Bit of a catch 22- isn’t it?
Noncompliance isn’t a word I like where consuming dangerous substances is concerned. My body- my decision- and it needs to be an informed one so I can weigh the risks and benefits. My doctor can guide me but that’s about all he can ultimately do.
It is the consumer they are selling to and they are implying that their customers are overly impressionable- but not if they buy the word of the company with blind faith- only if they have a bad reaction or a thought of their own.
Amazing
atlex
Salmon,
I have some understanding of labeling, but my comment goes way beyond labeling. Patients cannot be expected to properly interpret labeling. It is designed for professionals and, even then, I don’t think that many (or most) garden variety physicians can correctly interpret many parts of drug labels. We (as in all stakeholders in health care) have to figure out a way to communicate healthcare risks and benefits to patients. Labels just aren’t the appropriate means of doing so. There are some definite attempts in the past couple of years to create patient-friendly fair balance statements, but my sense is that these are rarely read. I think most patients pick up most of their knowledge out of context from media outlets that have little ability to put risk and benefit information in context.
One final note…you comment that you are “constantly fighting against being deceived by drug companies.” I would argue that in the vast majority of cases the drug company personnel you are dealing with are not attempting to deceive. They are putting up a vigorous argument for their point of view and typically have significant data supporting their view. You might view this data differently, which is fine. I happen to think that the tension in this interaction is a good thing.
Atlex
Just A Thought
“Patients cannot be expected to properly interpret labeling.”
Oh and we’re none to bright either. lol.
;)
Chris
Atlex -
If pharma companies are aware that “many (or most) garden variety physicians [can't] correctly interpret many parts of drug labels”, shouldn’t these companies be held accountable for this miscommunication? These companies have the market research resources to investigate how this information is being interpreted.
Salmon
Altex,
I have found clear evidence that drug companies do not report deaths as required by law.
When I ask drug companies for information they tell me you don’t need that.
When I look for something I have to drill down through 28 hyperlinks, to be told go somewhere else. to drill down through another 28 hyperlinks, only to have the process repeat several times. Finally finding a message that if you want the data call us.
You call the company and they promise to send you new stuff or clarification and when it finally arrives it says go look at the stuff we already gave you.
When you click on a hyperlink in a review they take you to the middle of another document in the wrong view size and when you finally figure out the document it’s a totally different clinical study than it’s supposed to be. Then there’s no way back to get to where you started from.
Now I agree in the vast majority of the time they don’t try to deceive. Why the other 40 studies that worked out fine for them I have no problems finding stuff, it’s only the study that has the really major safety signal where they try to deceive me, and this happens again and again and again with different companies.
If I have a meeting and I raise a potential safety signal before the meeting they just call up senior management and I have a baby sitter at the meeting from the very most senior level who simply tells the company they don’t have to look into this safety signal. Or I’m taken off the review.
Most safety issues are due to a toxic metabolite. So the metabolism studies are critical. Yet they are typically inappropriately done, broken up over multiple multiple different reports, structures aren’t given, changing code numbers are used, chemical structures aren’t adequately described and information is clearly missing, and it can take me 3 months to review this one critical study which I should be able to review in a couple of hours if it were written and presented properly. Same for QT studies where they claim there’s increases in liver function tests but then refuse to give me the labs, nor to they give me the data for how much drug is in the blood from half the subjects when the graphs clearly show many subjects have concentrations twice as high as the highest value in the data set.
The new reviewers are simply computer people and they crunch the numbers in the datasets without looking or withoung any consideration if the results are suspicious. This is the efficiency of the critical path.
Under the FDAAA 2007 all reviews have to be published as of I believe March 2007. Go look at the metabolism section of the clinical pharmacology review of tetrabenazine. Over 25 pages are redacted as ‘trade secrets’. There can’t be any trade secrets there. However in my expert opinion there’s enough information left in the review to show the sponsor did not fulfil the law and that the NDA was approved illegally.
Atlex either you have no clue what you’re talking about or you’re totally dishonest.
Salmon - A soon to be former FDA reviewer and whistleblower.
Opinions are my own and do not represent the opinions of the FDA.
atlex
JAT,
I think Salmon or anyone else with experience in the subject will confirm this…labeling is not designed for the layman. If it was, it would be written very differently. It’s not about being bright or not so bright.
Atlex
Salmon
Atlex,
If the data were even there. Your argument might have a chance. But they don’t even want to give me the data.
Salmon - Opinions are my own.
atlex
Salmon,
Since I have a clue what I’m talking about (and only commited the “sin” of disagreeing with you), I’ll view your last line as it was meant, an attempt to ridicule me. Give that, I’m not going to respond to your self-centered, paranoid diatribe. It deserves no additional consideration.
Atlex
Salmon
Atlex,
Some labeling is designed for the layman. I have examples of that where the companies clearly wanted to obfuscate a safety messages and how to take the drug properly.
Most labeling is for the professional that is always written in a way for marketing purposes. It is written in ways to hide things and to accentuate the positive. The studies are designed typically to provide misleading information.
In fact in many companies the labeling is written first by marketing with a few blanks for numbers and then the studies are done.
When I was in industry we would not infrequently have the marketing folk try to tell us what to put in the label even when the clinical data showed something different. According to my friends at other companies my company was one with the least problems in this regard.
It’s a big game and I suspect it’s part of your job to provide misinformation here.
Salmon Opinions are my own.
Salmon
Jaynesday,
We have trouble getting an honest label even initially. As for changes after I’m afraid there will always be problems. You need to analyze the data and there’s just too much to do in a real time manner and get out.
You need a mechanism to know what rare dangerouse to look for or a signal for a high frequency but high frequency is relative. Plus how do you look for a constellation of symptoms. Then you need to have internal discussions and then negotiations with the company.
It’ a good try but I’d rather leave this discussion to someone else.
Salmon - opinions are my own.
Salmon
Atlex,
You may try to take the high road. I’m simply sick and tired of dealing with dishonest people who want to run me in circles and overwhelm me. If my posts are showing that then excuse me. I’ve happened to have a very bad last 4 years. I’ve had my children threatened. I’ve been overwhelmed working nights and weekend. I’ve been repeatedly set up. I’ve had my career destroyed. I’ve tried to be honest and do the right thing and save the lives of hundreds of thousands of children. Only to be constantly harassed and needled and and set up by dishonest people who smile to your face while doing it. I grew up with suffering from severe ADHD and depressions. I’ve been placed under incredible stress not only by workload, but also legal actions. I Even had my coworkers tell me that I’m being monitored so that the second I show any emotions at all e-mails are to be sent to document it to build a case to fire me.
I’m certain that my postings here are being recorded to be used to show and say see he’s unbalanced. Well I’m going to stop responding to you because I simply don’t trust you. I don’t believe you have anything but an ulterior motive and don’t care at all for the patients.
Have and do I show emotion well yes and if I’m testy today it’s only because I was fired yesterday for going to Congress and the FBI.
Now with me fired some of those drugs whose approvals have been delayed I suspect will now shortly be approved and nonapprovals will be resubmitted. They’ve done it with other reviewers in the past.
Opinions are my own.
Salmon
Convenient with this whole WSJ article is an FDA presentaion at the Epilepsy Society meeting that there is an increase in suicides on antiepileptics. It looks to me like the data collection and presentation was designed to create exactly this kind of problem at exactly the right time with the preemption case.
It sure does play into the drug company’s agenda doesn’t it?
Salmon - Opinions are my own
atlex
Chris,
Labeling is under the control of the FDA. Although there may be disagreement as to how much freedom a pharma company has in the specifics of the label, all labeling language still must go through the FDA and fit regulatory and legal requirements. Unfortunately, as labeling has evolved, no one–the FDA, Congress, pharma companies, activists–has taken a good hard look at how to best communicate information to “garden variety” professionals. This is not an attempt to hide or minimize warnings or risks, but simply a recognition that there must be a better way to both design labels and, more importantly, a better way to communicate information to those who are intended to use it.
Atlex
Chris
> no one–the FDA, Congress, pharma companies, activists–has taken a good hard look at how to best communicate information to “garden variety” professionals
Atlex -
OK, so we seem to agree that it is not done. Why not? While difficult to do on a global basis, this could easily be done on a drug by drug basis.
Even within the existing labeling framework, pharmaceutical companies have the resources to make sure what is in the label is communicating effectively to “garden variety” physicians. Mullions and millions of dollars are spent on market research for promotions. What is to prevent a company from using this methodology to help draft selected portions of the labeling for FDA approval? Also, what is to prevent companies from assessing the effectiveness of the labeling in communication important safety information? In essence, this is not done.
Jaynesday
Salmon, sorry to hear about your employment situation. I commend your bravery and commitment to our health safety. From reading your posts here it is obvious you have a singular purpose – to do your job to the best of your ability and to stay true to the oath for drug safety that you took on our behalf. I hope you can continue to fight the good fight and please know that you are not alone.
Anon.
Let’s see if anyone from Congress who claims that they’re interested in FDA even looks into it.
Just A Thought
What Jaynesday said.
Thanks, Salmon.
Justice in Michigan
Belated response to Atlex - Fully agree that the average person doesn’t know the stories. That’s why I wrote: “the average person following the stories comes away cynically.” The operative and deliberate phrase was “following the stories.”
What I think remains a question - for those people - is how to put such stories into the wider context of compliance, and decide what is typical re: the balance between honest scientific debate and the various ways deception happens. There is also a critical difference, I think, between honest disagreement and, in essence, a “cat & mouse” approach: i.e., it’s there, just see if FDA can find it. In any case, my goal is not to find “sins,” but to genuinely understand what are outlier circumstances and what is normative.
Re: Jaynesday’s question, there are European “pharmacovigilance” systems that often do a better job than we do identifying AEs closer to “real time.” I’ll look for a reference for you.
Justice in Michigan
Chris writes: “Millions and millions of dollars are spent on market research for promotions. What is to prevent a company from using this methodology to help draft selected portions of the labeling for FDA approval? Also, what is to prevent companies from assessing the effectiveness of the labeling in communication important safety information? In essence, this is not done.”
Critical point, in my view. The question that arises is whether, in the competitive environment as it exists, how far away are we from this happening?
George
Re above comment:
“Since I have a clue what I’m talking about (and only commited the “sin” of disagreeing with you), I’ll view your last line as it was meant, an attempt to ridicule me. Give that, I’m not going to respond to your self-centered, paranoid diatribe. It deserves no additional consideration.
Atlex”
I remember this post from Atlex
“Neil,
Your statement, coming from a psychologist, sounds highly biased. Wouldn’t an equivalent statement from an academic psychiatrist who disagrees with you be that the reason that psychologists become psychologists is because they couldn’t hack medical school?
Atlex”
Sounds like Atlex likes to really give it, but can’t take an honest assessment of himself.
Lisa Van S
Atlex,
“The Nutty Fringe”,.. I am going to take that as a compliment!!
” Labeling is under the control of the FDA,.. OMG.. how funny is that!!. The Medication Guide issue, is a perfect example of how the FDA bows to pressure from the A.P.A, One of Industry’s most infamous apologists.
“You specialize in adherence programs” Wow,.. That sure says it all doesnt it. Keep on pushing the Paxil for kids, No Safety,.. No Efficacy, but what the hell, adhere,.. comply. Thousands of dead children, who cares,.. Just Adhere, because you and others say so..
Lisa Van S
Atlex,
“Patients cannot be expected to properly interpret labeling designed for professionals”
I did alright,.. I understood, except suicide wasnt in the paxil label, it is now. My advice to patients… purchase a magnifying glass, and read the PI. Never underestimate the unconditional love a parent has for their child.
atlex
Lisa,
My contention was and is that labels are far from reader friendly even for professionals. And, despite your statement any communications expert will tell you that labels are written far above the reading comprehension level of most laypersons. By the way, they probably should be in order to provide the information that should be conveyed to professionals. Wouldn’t it be far better to have well written patient oriented labels that provide full disclosure but at a reading level that can be understood by the layperson and in a way to put both benefits and risks in the proper context? The alternative is to continue to have most healthcare information come from the media which tend to make every treatment benefit sound like the best thing since sliced bread and every treatment risk, even the rare ones, seem as though it happens to everyone. I think that we are in agreement that we want patients to have all of the information they need to make treatment decisions communicated in a manner that can be as easily understood as possible.
Finally, Lisa, I didn’t say that I specialize in adherence programs, I said that there was one point in my career when I developed content for adherence programs. Your comment regarding me says a lot. You’ve jumped from me developing content for adherence programs (mostly associated with hypertension, diabetes and Parkinson’s disease) to an accusation that I am “pushing the Paxil for kids…thousands of dead children.” I’ll leave it to others to determine whether that qualifies as a little bit nutty.
Salmon
As an expert I can say that drug company written labels are so obtuse that even I can’t understand them even with the data from the companies that isn’t otherwise available because the critical data is simply not submitted or explanations of the true meaning is not given and instead is explained away with false reasoning. It’s only now that I’ve begun to realize how many hidden things there really are in labeling.
Atlex’s proposal in essence seems to me to be let the industry have preemption and then an only then will industry actually make the side effects and problems more clear in the labeling. Even with that I don’t see it happening to the full extent needed. Because the labeling with adverse events, warnings, and precautions, will minimize market uptake and so companies will delay until as long as possible. This is what companies are truly worried about overwarning.
What they are doing now is saying give us preemption and we’ll say things like yes there are bone fracture problems and suicides for some drugs in the class but we don’t want to say which ones are the really problematic ones so we’ll put a little something in saying well it’s been observed with some drugs in the class so be aware of the possibility with this one too but it’s up to you if you want to take it
This is exactly the approach companies take with long term usage saying; ‘Well it hasn’t been studied but if you decide to do it you should reevaluate occassionally’. Meanwhile they know that there’s long term cardiac toxicity or other problems like bone fractures.
The bottom line in my opinion is give the FDA reviewers all the information and also not have FDA management hide the big picture or prevent us from doing reviews. Then let us try to write reasonable and balanced labeling. If we could actually do that then I think the companies might actually sometimes have a valid defense based on preemption. But this will still need to be determined on a case by case basis. However let the facts be examined each time and a court decide and not make it a blanket determination.
Salmon
Opinions are my own and do not represent the FDA.
Nathan
Is it a prerequisite that employees of the FDA are paranoid? It seems that both Salmon and FDA reviewer seem to believe that their management is spying on them and ready to stab them in the back at any moment. They both also believe that those of us in industry are constantly hiding data and trying to pull one over on them. I’m beginning to think that both paranoia’s just exist in their own mind…
As Atlex states, disagreements about the interpretation of results does not necessarily imply dishonesty or malevolence.
We (in the pharma industry) often believe that the FDA undervalues efficacy while overemphasizing safety. The FDA believes (often) that industry overvalues efficacy and undervalues safety. Who is correct? It’s a value judgment – both can be correct at times. Reality is probably somewhere in the middle.
The FDA does not have a monopoly on honest scientists. Nor do they have a monopoly on safety experts. While you (the FDA) are the final authority, you are not the only experts in this field. You seem to forget that well educated and honest people can have an honest disagreement about the interpritation of safety signals.
– it seems to me the personal paranoia that you describe (
Salmon
Nathan,
I will thank you for not using ad hominum attacks.
I have absolutely no problem with arguing data and having honest scientific disagreements and there are many honest people in industry. However to do this I need to have the data submitted first. the frequency with which companies refuse to provide data does not support your argument.
I worked at a major pharmaceutical company in regulatory affairs prior to going to going to FDA I can attest from the industry side that yes data is withheld even when it is specifically asked for.
There is a lot of corruption and I will allow the legal system to determine if my concerns regarding my management are justified or not. Since collusion between Drug companies and FDA managemenet have been documented by Congress for so many other FDA reviewers. (John Guegerian, Leo Lutwack, Bob Misbin, JoAnn Liang, David Graham, Victoria Hampshire, Andy Mosholder, Bob Prizont). Why won’t you even admit the possibility that it could happen to someone else. So please do not prejudge.
As for paranoia you can get a little paranoind and sometimes make mistakes about motive but be correct the other 90% of the time. As they say just because you’re paranoid doesn’t mean they aren’t out to get you.
Yes there are industry experts. For example Joseph Biederman, and others.
I’m certain many people here believe he has just as much interest in safety as I do as a parent of a child.
If you look at many websites industry frequently tries to show that anyone who doesn’t agree is a ‘wack job’ and intimidate them. Well I don’t say there is no such diseases, I don’t say the drugs don’t work, I don’t say that the drugs are totally bad, I don’t say that the drug companies are all evil, I even understand that although the term chemical imbalance is not perfectly correct that it does have some utility.
I’m an expert in these drugs and I look at the data, and when I look at the data I have real concerns.
If the pharmaceutical companies have a disagreement with my conclusions. Then I’m perfectly willing to show my analyses and conclusions to the world and to allow for peer review. All the drug companies have to do is allow all the information to be made public.
So I put out a challange to Lilly.
Lilly, please allow the publication of all information (including submissions and IND and NDA reviews) on Zyprexa, Symbyax, and Cymbalta including data from other studies from other sponsors about your drugs.
Here is only one drug company and three drugs. Let’s have an open examination of the data.
I’m willing to put up or shut up Nathan, I’m willing to show that I can build an argument based on the data and to allow for open peer review (and not just some hand selected people who are biased to the hands that feed them). Now you get Lilly, or you can pick a different company where I can examine the data and reviews.
I think it would be best if we take some other psych drug that’s been turned down in the last few years and the company has complained about the FDA in the press. I think that would be best. I seem to recall Bifeprunox (solvay and Wyeth) and Modafinil (Cephalon).
Opinions are my own
Person
Its a necessary evil or else the blind know not they walk on the cliff edge.
Person
Surely if there where no black box warnings people wouldn’t know before hand a side effect of killing themself may occur?
Justice in Michigan
I will just add this.
No genuine reform will come unless a range of folks inside _both_ industry and FDA find a way to speak freely about what they know. We are obviously lightyears away from that.
But, were it to happen, we might not even need lawsuits to ferret out the truth in some instances. As I have related before, even though I am anti-preemption, I know that truly exploitative lawsuits (and there certainly are those) can have a chilling effect on those in industry who _might_ be willing to challenge company policy in some instances.
Likewise, it would be fairly difficult to live in these conditions and not be some version of “paranoid” - not in the DSM sense, but in the old Soviet Union sense.
Mike
As to the comment about byetta, for the number of cases that had pancreatitis you have to look more closely at those cases, in that most had other more serious contributory risk factors, such as cancer, severe obesity(numerous indications and drugs taking), and gall bladder surgery, for those that died. I believe that the company that makes the drug was doing a strict count in order to show that their drug was no more of a risk to cause pancreatitis than other drugs and those cases discovered possibly backfired and a PR was required. Since then they have said that a major insurance carrier has proven that the byetta is no more likely a cause of pancreatitis than other drugs used by type II diabetics. And you have to keep in mind that pancreatitis is more common in diabetics and over 800 or so die every day. I believe there should be more information given to the patient of course such as via the doctor in person with the patient, but if you cover every possible side effect and then break down the small % for each one, then the patient will just be overloaded with information. There are very common side effects such as nausea and headache and then many other possibles, and then when you get down to more severe, to include death, the % is so small for most drugs, that anyone with common sense and seeing the benefit of the drug will chose the drug, but of course with a drug like byetta or other with a chance of association, if the patient really wanted to know, the information is and has been available, just that not all physicians, PAs, nurses, and pharmacists will not all break out the PPI inserts and scroll down thru all the many side effects after passing the MOA and indications and interactions and warnings to tell you about it(but be sure and read your information received from the pharmacy). And for the the few people that happen to die each year from the flu, are you going to attempt to blame that on a drug called Januvia, just because it can possible cause flu like symptoms and maybe weaken your immune system, and oh, maybe the physician did give you a higher dose than usual. And what about that….how many of those on byetta were given the drug off label for weight loss, or a higher dose that the manufacturer recommends? But since the risk for pancreatitis is so small, I would sure like to know how many of those on a higher dose, are probably not even bothered by it, since for so many people it actually improves your health and type II diabetes while lowering your weight(for many). Also, how does allowing those loud lawyers with 800 numbers begging you to call, help in the inform and consent realm, except to offer suggestion that you might be sicker than you are, but probably not as sick as them….lol. Do they ever give up? I even heard one of their ads trying to find sufferers from a weakened ankle tendon after using Cipro, a side effect so rare, you are more likely to die from a lightening strike!
James R
To the WSJ! You write about one patient who had a bad reaction to Chantix. Exactly how many patients have told you of these bad reactions, or can you at least give me your good guess on this. I have been reading about thousands who have had severe reactions to Chantix; on this site. Is this patient “one of many” or “one of thousands” who contacted you personally with their story? I know the FDA Medwatch program “blew up” with reports about severe reactions to Chantix about a year ago. I was one of them. I also came to this site and reported it. So now there are at least two patients, out of I-don’t-know-how-many, who have reported severe reactions with Chantix to the WSJ.